Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS
| Autor: | B. J. A. Goense, Marjan A. Versnel, Henk C. Hoogsteden, M. M. Verheggen, A. O. Brinkmann, P. W. C. Adriaansen-Soeting, P. T. W. Van Hal |
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| Rok vydání: | 1996 |
| Předmět: |
Electrophoresis
Lipopolysaccharides Pulmonary and Respiratory Medicine medicine.medical_specialty medicine.medical_treatment Cell Bronchi Simian virus 40 Biology Ligands Dexamethasone Epithelium Translocation Genetic Adenoviridae Cell Line Receptors Glucocorticoid Glucocorticoid receptor Internal medicine medicine Humans RNA Messenger Receptor Glucocorticoids Cell Line Transformed Tumor Necrosis Factor-alpha DNA medicine.anatomical_structure Cytokine Endocrinology Gene Expression Regulation Cell culture Tumor necrosis factor alpha Inflammation Mediators Glucocorticoid Interleukin-1 medicine.drug |
| Zdroj: | European Respiratory Journal. 9:2036-2043 |
| ISSN: | 1399-3003 0903-1936 |
| DOI: | 10.1183/09031936.96.09102036 |
| Popis: | Bronchial epithelium plays a major role in the regulation of inflammatory reactions in the airways. It is thought to be a possible target for glucocorticoid therapy. Glucocorticoid responsiveness requires the presence of specific glucocorticoid receptors (GR). Until now, little was known about the presence of such receptors in the human bronchial epithelium. In this study we demonstrated the expression of GR messenger ribonucleic acid (mRNA) in two simian virus (SV)-40/adenovirus-transformed human bronchial epithelial cell lines, BEAS S6 and BEAS 2B. In a whole cell dexamethasone binding assay, BEAS S6 and BEAS 2B cells were found to possess (mean +/- SEM) 28.9 +/- 4.4 x 10(3) and 32.1 +/- 5.7 x 10(3) binding sites per cell, respectively, with dissociation constant (Kd) values of 8.2 +/- 1.5 and 8.6 +/- 2.4 nM, respectively. Using electrophoretic mobility shift assays we demonstrated the binding of nuclear translocated GR to specific sites on deoxyribonucleic acid (DNA), named glucocorticoid responsive elements (GRE). Lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta) significantly increased the number of GR per cell (median = 312% and 171% of control, respectively; p < 0.05), but significantly reduced the ligand affinity of these receptors, i.e. increased the Kd (median = 410% and 145% of control, respectively; p < 0.05) in BEAS 2B cells. These results indicate that the bronchial epithelium may be an actual target for glucocorticoid therapy. Inflammatory mediators, such as IL-1 beta and LPS, modulate the number and ligand affinity of these GR. Therefore, the response of bronchial epithelium to glucocorticoid therapy may be modulated by airway diseases associated with inflammation. |
| Databáze: | OpenAIRE |
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